Studies of patients with various genetic disorders are being conducted. There is emphasis on detection of chromosomal variations and their relationship to phenotypic abnormalitites segregating with families. Chromosomal findings are also correlated with specific genetic markers such as HLA and alpha-1-antitrypsin. Diseases with possible multifactorial etiology have been studied to determine if they are associated with either primary (constitutional) or secondary chromosomal abnormalities. One goal is to determine if consistent chromosomal alterations can be utilized for diagnosis or to assess disease progression. Previous studies of the Fragile X syndrome, Alzheimer disease, and Down syndrome are continuing, and protocols for studies of Down syndrome parents and individuals with mental illness were recently initiated. More limited cytogenetic studies of individual patients or small families with other syndromes of interest to colleagues in the Genetics Program were carried out: the Prader-Willi syndrome, familial aniridia, pseudohypoparathyroidism, familial premature menopause, and endocrine disorders with abnormal sexual differentiation and development. Methods utilized include routine peripheral blood and tissue culturing, analysis of chromosomal response to folate-thymidine deprivation (fragile site induction), in-situ silver staining for detection of ribosomal gene activity of nucleolus organizing regions, chromosomal banding with Giemsa-tryspin or fluorescent stains, and methotrexate synchronization for analysis of prometaphase banding patterns. All information is correlated with results of clinical studies and frequently utilized in genetic counseling. Screening of relatives may be done to determine if carrier status of chromosomal variations is associated with phenotypic abnormalities. Significance of variations can be assessed best by complete family studies, and the value of specific types of chromosomal analysis for diagnosis determined.